1. Field of the Invention
The present invention relates generally to the preparation and use of tissue adhesives which rely on combining fibrinogen and thrombin. More particularly, the present invention relates to a method for preparing a fibrin glue from plasma components obtained from a single donor, preferably for use in autologous fibrin glues.
Tissue adhesives in the form of fibrin glues have been proposed for use to control bleeding and promote wound healing in a variety of traumatic and surgical situations. Many wounds and surgically created defects are not amenable to conventional suture repair, and the ability to enhance defect closure and inhibit bleeding by promoting clot formation would be advantageous. Fibrin glues contain fibrinogen and thrombin which, when mixed together, form fibrin, the basic substance of clot. In Europe and elsewhere, commercial fibrin glues are prepared from fibrinogen obtained by pooling plasma cryoprecipitate from multiple human donors. The risk of disease associated from such pooled plasma sources, however, has caused such products to be withdrawn from use in the United States.
In order to avoid the risk associated with pooled plasma sources, "autologous " fibrin glues have been proposed where fibrinogen is obtained from plasma from a single donor, often a patient to be treated in a subsequent surgical procedure. Such autologous fibrin glues, however, rely on combining the autologous fibrinogen with bovine thrombin, and thus suffer from the deficiencies associated with use of non-human animal products e.g., an immune response against the bovine plasma proteins.
Prior to the work reported in the present application, it was not apparent that thrombin, as well as fibrinogen, could be obtained from single donor plasma. In particular, it was not apparent that sufficient thrombin could be obtained from the amount of plasma used as a source for the single donor fibrinogen. Furthermore, it would have been expected that thrombin obtained from clotted plasma would be inactivated by plasma antithrombins and would therefore not be suitable for subsequent use in a fibrin glue.
For these reasons, it would be desirable to provide improved fibrin glues and methods for their preparation and use, where the fibrin glues are prepared from fibrinogen and thrombin components obtained from single donor plasma, preferably for use in autologous compositions where the glue is later administered to the donor. It would further be desirable that the thrombin component of such fibrin glues contain sufficient thrombin to produce a solid fibrin gel when mixed with the fibrinogen component, and that the thrombin component remain stable and capable of producing the fibrin gel for at least an hour after preparation.
2. Description of the Background Art
Wiegand et al. (1994) Head & Neck November/December, pages 569-573, describes the preparation and use of a fibrin glue having a fibrinogen component obtained by cryoprecipitation of single donor plasma and a bovine thrombin component. The shortcomings of such fibrin glues are discussed in Cederholm--Williams (1994) The Lancet 344: 336-337. Review articles discussing various forms of fibrin glue include McCarthy (1993) Transfusion Med. Rev. VII: 173-179; DePalma et al. (1993) Transfusion 33: 717-720; and Brennan (1991) Blood Reviews 5: 240-244. U.S. Pat. No. 4,627,879, describes the preparation of fibrinogen by cryoprecipitation of plasma from a single donor. While combination with "human " thrombin is suggested, no source of technique for obtaining human thrombin is provided, and the only specific source of thrombin mentioned is commercial bovine thrombin. Other U.S. Patents relating to tissue adhesives include U.S. Pat. Nos. 4,909,251; 4,655,211; 4,453,939; 4,442,655; 4,427,651; 4,427,650; 4,414,976; 4,377,572 4,362,567; 4,298,598; and 4,265,233.